Published online Jun 7, 2015. doi: 10.3748/wjg.v21.i21.6745
Peer-review started: December 5, 2014
First decision: January 22, 2015
Revised: January 30, 2015
Accepted: April 28, 2015
Article in press: April 28, 2015
Published online: June 7, 2015
AIM: To determine whether or not the use of antioxidant supplementation aids in the prevention of post- endoscopic retrograde cholangiopancreatography pancreatitis.
METHODS: A systematic review of randomized controlled trials (RCTs) was made to evaluate the preventive effect of prophylactic antioxidant supplementation in post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP). The inclusion criteria included: acute post-endoscopic retrograde cholangiopancreatography pancreatitis in adults; randomized clinical trials with the use of any antioxidant as an intervention compared with placebo, to reduce PEP. The outcome measure was the incidence and severity of PEP. Twelve RCTs involving 3110 patients since 1999 were included. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), N-acetylcysteine (NAC) in three trials, and allopurinol in six trials. The group of patients treated with NAC received different doses; either oral or intravenous, and allopurinol-treated patients received five different oral doses in two different administration periods. The results are expressed with raw numbers, proportions, as well as mean and standard deviations. The incidence of pancreatitis between groups was analyzed with Pearson’s χ2 test or Fisher’s exact test (F). The main outcome is expressed as relative risks and 95%CI.
RESULTS: The incidence of pancreatitis in all antioxidant treatment groups was 8.6%, whereas it was 9.7% in the control group. The antioxidants used were selenite, β-carotene, and pentoxifylline (each one in one trial), NAC in three trials, and allopurinol in six trials. In allopurinol trials, three different dosifications were used; two trials reported a low dosage (of less than 400 mg), two trials reported a moderate dose (600 mg) and the remaining two employed higher doses (more than 900 mg). Supplementation was not associated with a significant reduction in the incidence of PEP [relative risk (RR) = 0.93; 95%CI: 0.82-1.06; P = 0.28]. In addition, the incidences of PEP in patients treated with allopurinol and those treated with other antioxidants were similar to that observed in patients who received the placebo (RR for trials with allopurinol, 0.92; 95%CI: 0.78-1.08; P = 0.31) and, with the use of other antioxidants, the incidence of PEP was 8.9%, whereas it was 9.7% in the control group (RR = 0.95; 95%CI: 0.77-1.18; P = 0.19).
CONCLUSION: Antioxidant supplementation shows no beneficial effect on the incidence of PEP. There is a lack of robust trials to support the use of antioxidants for prevention.
Core tip: Acute pancreatitis is considered one of the most serious complications after endoscopic retrograde cholangiopancreatography (ERCP). The mechanism of post-ERCP pancreatitis remains unclear but several studies show that free radicals play a role in its pathogenesis. Antioxidant drugs have been tested using different routes of administration and dosifications. The analysis of all randomized clinical trials published since 1999 did not revealed any significant reduction in the incidence and severity of post-endoscopic retrograde cholangiopancreatography pancreatitis (PEP) when compared with placebo. There is currently a lack of robust trials to support the use of antioxidants for the prevention of PEP. Well-designed placebo-controlled randomized controlled trials are warranted to determine any beneficial effect.